Researchers have reported rapidly isolating and analyzing about 350 antibodies from a survivor of the 2014/2015 West African Ebola outbreak. The work provides insights into the immune response to the virus that could be useful for drug discovery and vaccine efforts, and the speed with which it was conducted offers a solution to the technical problems that hamper rapid responses to emerging infections.
Characterizing patient antibodies "in the past . . . took over a year, and you may have ended up with a dozen antibodies," co-author Tillman Gerngross told BioWorld Today.
In contrast, the method developed by Gerngross, corresponding author Laura Walker and their co-authors delivered 350 such antibodies in six weeks a time frame that "cuts about a year off of previous timelines," Walker told BioWorld Today.
That time can be critical not just for the deaths and suffering that can be prevented by more rapid drug or vaccine development. In the case of Ebola virus, the time course of the West African outbreak was such that by the time clinical vaccine candidates entered the field, new cases were rare enough to make demonstrating vaccine efficacy a challenge. (See BioWorld Today, May 13, 2015.)
In terms of their ability to fight disease, antibodies can range from ineffective to neutralizing, or capable of binding a virus and preventing it from infecting cells.
Neutralizing antibodies and ideally broadly neutralizing antibodies, which are capable of taking out multiple different viral strains are of critical importance for vaccine development, where they give clues to which sorts of antigens a successful vaccine needs to contain. In diseases where a vaccine has so far proved elusive, including HIV, there are also attempts under way to develop passive antibody administration as a therapeutic strategy. (See BioWorld Today, April 4, 2013.)
In their studies, which they published in the Feb. 19, 2016, issue of Science, the authors Gerngross, who is the co-founder and CEO of Adimab LLC; Walker, a scientist at Adimab; and their colleagues in academia and the military profiled the anti-Ebola antibody repertoire of a patient who had survived infection with the 2014 Zaire strain of Ebola.
The key to the method described by Walker and her colleagues is that part of the process is done in yeast rather than mammalian cells, as is the case with other characterization methods.
Using their method, the authors were able to identify antibodies that bound to every known antibody binding site of the Ebola virus. They also identified a particular region within the viral stalk protein as a promising target for highly potent antibodies.
While a large fraction of antibodies tend to be neutralizing in other viral infections, such as influenza and even HIV infections, in Ebola the proportion of neutralizing antibodies is generally lower.
The patient whose antibody repertoire the team used for their studies had an unexpectedly high proportion of neutralizing antibodies more than three-quarters of his antibodies were neutralizing. Only 5 percent, however, were "extraordinarily potent" a proportion which illustrates why it is so advantageous to be able to look at many antibodies. "The only way to isolate the potent ones is to get lots of them overall," Walker said.
The authors plan to make the sequences of all antibodies described in their study available through public databases, providing a resource for Ebola drug and vaccine developers.
More broadly, the method can solve one of the technical problems in responding to emerging infectious diseases.
"Every time we have a new emerging pandemic, it's the same story," Gerngross said.
"What we've taken off the table with this paper is the technical discussion . . . shifting the focus back" to how to develop a comprehensive strategy for how to fight emerging infectious diseases, in particular the balance between which diseases are currently most urgent and which are the greatest long-term threats.
Such a comprehensive strategy is also lacking, and Gerngross said that though Adimab wants to be part of such a comprehensive solution, the leadership there will need to fall to others. "Putting it all together is a political question, not a scientific one," he said.
The political challenges of responding to emerging infectious threats have been on display this week, as a political battle is playing out in Washington over whether to use funds once allocated to Ebola to continue to push vaccine and therapeutics development for that disease, or to shift them to the virus that has eclipsed Ebola in the near term Zika virus.
But as far as the scientific underpinnings of a rapid response, Gerngross said, his team's work has demonstrated that "there is a way of solving this problem."